title: Effect of buffer general acid-base catalysis on the stereoselectivity of ester and thioester H/D exchange in D2O.
abstract: As part of a comprehensive investigation on the stereochemistry of base-catalyzed 1,2-elimination and H/D exchange reactions of carbonyl compounds, we have found that the stereoselectivity of H/D exchange of 3-hydroxybutyryl N-acetylcysteamine (3) in D(2)O is strongly influenced by the presence of buffers. This buffer effect is also operative with a simple acyclic ester, ethyl 3-methoxybutanoate (7). Buffers whose general-acid components are cyclic tertiary ammonium ions are particularly effective in changing the stereoselectivity. (2)H NMR analysis showed that without buffer, H/D exchange of 3 produces 81-82% of the 2R*, 3R* diastereomer of 2-deuterio 3 (the anti product). In the presence of 0.33 M 3-quinuclidinone buffer, only 44% of the 2R*, 3R* diastereomer was formed. With ester 7, the stereoselectivity went from 93-94% in DO(-)/D(2)O to 60% in the presence of buffer. Phosphate buffer, as well as others, also showed substantial effects. The results are put into the context of what is known about the mechanism of H/D exchange of esters and thioesters, and the relevance of the buffer effect on the mechanism of the enoyl-CoA hydratase reaction is discussed. It is likely that hydrogen bonding in the enolate-buffer acid encounter complex is an important stereochemical determinant in producing a greater amount of the 2R*, 3S* diastereomer (the syn product). Studies that involve the protonation of enolate anions in D(2)O need to include the buffer general acid in any understanding of the stereoselectivity.
authors.affiliation: Department of Chemistry, Carleton College, Northfield, Minnesota 55057, USA. jmohrig@carleton.edu
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mohrig
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Reiter
authors.forename: Randy
authors.initials: R
authors.lastname: Kirk
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Zawadski
authors.forename: Nathan
authors.initials: N
authors.lastname: Lamarre-Vincent
mesh_terms: D000143:Acids / Q000737:chemistry*; D002384:Catalysis; D041961:Deuterium Exchange Measurement; D017666:Deuterium Oxide / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000143:Acids; D004952:Esters; D017666:Deuterium Oxide